Radioisotopes in action Diagnostic application of radioisotopes Steps of diagnostic procedure - Radioactive material introduced into the patient - Distribution and alteration of activity is detected -Monitoring of physiological pathways and/or identification and localization of pathological changes Information from various medical imaging techniques Structure X-ray Ultrahang MRI differences according to the different physical parameters / properties of tissues X-ray Isotope diagnostics Function Isotope diagnostics MRI dynamic physiological / metabolic processes of different body organs can be followed Shows the structure Report the metabolic activity
Father of Nuclear Medicine George Hevesy and his landlady Georg Charles de Hevesy (1885-1966) Nobel Prize in Chemistry 1943 for his work on the use of isotopes as tracers in the study of chemical processes In any event, he became convinced that his landlady had a nasty habit of recycling food. Hevesy secretly spiked the leftovers on his plate with radioactive material. A few days later, the electroscope he smuggled into the dining room revealed the presence of the tracer The choice of the appropriate radioisotope for nuclear imaging Maximize the information Minimize the risk. For that find the optimal type of radiation photon energy half-life Type of radiation α β γ decay via photon emission to minimize absorption effects in body tissue Only γ-radiation has sufficient penetration distance. radiopharmacon purely gamma-emitting isotope would be preferable
photon energy Low-energy photon High-energy photon hf > 50 kev Photon must have sufficient energy to penetrate body tissue with minimal attenuation BUT! Photon must have sufficiently low energy to be registered efficiently in detector and to allow the efficient use of lead collimator systems (must be absorbed in lead) a suitable physical half-life Λ = λn smaller is better but the value is limited from below e.g., by the sensitivity of the detector 0,693 = N T shorter is better smaller is better dosimetric considerations for patients but it has to be long enough for monitoring the physiological organ functions to be studied radiopharmaceutical is substance that contain one or more radioactive atoms and are used for diagnosis or treatment of disease. It is typically made of two components, the radionuclide and the chemical compound to which it is bound. Basic requirements: specific localizing properties; high target : non-target ratio have no pharmacological or toxicological effects which may interfere with the organ function under study. A number of factors is responsible for the ultimate distribution of the radioisotope: blood flow (percent cardiac input/output of a specific organ) availability of compound to tissue, or the proportion of the tracer that is bound to proteins in the blood basic shape, size, and solubility of molecule which controls its diffusion capabilities through body membranes
examples pharmaceutical radioisotope activity (MBq) Pertechnetate Tc 550-1200 target organ brain Pirophosphate Tc 400-600 heart Diethylene Triamine Penta Acetic Acid (DTPA) Mercaptoacetyltriglycine (MAG3) Methylene Diphosphonate (MDP) Tc 20-40 lung Tc 50-400 kidney Tc 350-750 bones Optimal activity for diagnostic procedure Maximize the information Minimize the risk Λ ~ 100 MBq Types of images Static picture spatial distribution of isotope / activity at a certain time Dynamic picture variation of the amount of isotope / activity in time Static and dynamic picture series of static recordings Types of images Static picture spatial distribution of isotope / activity at a certain time Emission CT SPECT (Single Photon Emission Computed Tomography) PET (Positron Emission Tomography) thyroid glands Isotope accumulation in kidneys
Λ(MBq) Λ max Types of images Dynamic picture variation of the amount of isotope / activity in time 50 40 30 20 Effective half -life activity decreases by half in the target organ Λ(MBq) Λ max 50 40 30 20 10 0 0 15 30 45 60 75 90 t(min) T eff Effective half-life activity decreases bay half in the target organ λ Λ = Λ effective 0 e ( λ = λ phys phys +λ biol + λ )t biol 10 0 0 15 30 45 60 75 90 t(min) T eff 1 T eff = 1 T phys + 1 T biol example Right kidney Left kidney The final fate of the radiotracer depends on how the addressed organ deals with the molecule, whether it is absorbed, broken down by intracellular chemical processes or whether it exits from the cells and is removed by kidney or liver processes. These processes determine the biological half-life T biol of the radiopharmaceutical. kidney Isotope accumulation
example Thyroid glands Isotope accumulation Gamma camera cc 40 cm Hal Anger 1920-2005 Photomultiplier tubes Scintillation crystal Collimator Hal Anger and coworkers 1952
A radioactive source emits gamma ray photons in all directions. collimator Scintillation crystal NaI(Tl) Sufficient detection efficiency photons of 150 kev μ ~2.2 1/cm 10 mm thickness ~ 90% attenuation Proper wavelength 415 nm for PM photocathode Collimators are composed of thousands of precisely aligned channels made of lead. The collimator conveys only those photons traveling directly along the long axis of each hole. Photons emitted in other directions are absorbed by the septa between the holes. Problems: fragile temperature sensitive hygroscopic Size and geometry of holes are essential for the resolution. Photomultiplier tubes Pulse amplitude spectrum Amplitude of an electric pulse generated by a γ-photon absorption in photoeffect is proportion to the photon energy. channel Transformation of light pulses to electric signal. Typically 37-91 tubes, 5.1-7.6 cm diameter each Amplitude of electric pulses varies in a wide range, because - absorption of one γ-photon induces electric signals in more then one tubes. - attenuation mechanism can be photoeffect and Compton-scatter. γ-photon position Light patch PM tubes photopeak These electric pulses can be distinguished by discrimination (DD).
Gamma camera Pertechnetate (intravenous 80 MBq) distribution in thyroid glands Photomultiplier tubes Scintillation crystal Collimátor normal struma diffusa struma multinodularis Identification of source position is facilitated by the collimator the PM tubes the discrimination. Cold nodules Liver lesion nodules Bone scintigraphy Tc-MDP: 600 MBq Tc- fyton normal imaging in bone metastases
Gamma camera space and time distribution can be recorded Gamma camera image: summation image static and dynamic pictures can be reconstructed Camera parameters: spatial resolution energy resolution efficiency of detection For depth resolution: tomographic device is necessary SPECT Single Photon Emission Computed Tomography SPECT Tomographic application of γ-cameras data collection in 360. Cross-sectional image can be reconstructed. Measurement from a series of projections. Computer directs the movement of the detector, stores the data, reconstruct the cross-sectional image Variouos camera arrangements
SPECT images of scalp PET Positron Emission Tomography Tc- HMPAO coincidence processing unit dataprocessing coincidence processing Isotope distribution Channel 1 Channel 2 Summed channel annihilation Coincidence events image reconstruction
The most frequently used radionuclides in PET are radioisotopes of structural elements of natural organic molecules. PET/CT Combination of structural and functional imaging Isotope manufacturing nearby the site of application (see half-lives). Activity of brain areas CT PET PET/CT PET In rest hearing vision
Radiation therapy Radiotherapy : ionizing radiation induces damages at molecular and cellular level. This can be beneficial against tumour tissues 1. Which radiation is the best? 2. What is the optimal dose of radiation? 3. What is the best technique for generation radiation? 4. Irradiation selectivity protection of healthy structures? Approaches Palliative radiotherapy to reduce pain and address acute symptoms e.g. bone metastasis, spinal cord compression etc., Radical radiotherapy as primary modality for cure e.g. head and neck Adjuvant treatment in conjunction with surgery e.g. breast cancer α β -, e-, γ, Rtg, p n Internally deposited radioactivity Linear ion density: the amount of ion pairs in a line generated in a unit distance (n/l) LET (Linear Energy Transfer : the energy transferred to the material surrounding the particle track, by means of secondary electrons. (ne ionpair /l) In the air: E ionpair =34 ev ionpair distance (cm)
α β - : e - : γ, Rtg, p n Particle energy is not optimal continuous energy spectrum typical energy: few MeV accelerated electron - 10-20 MeV production: linear accelerator Internally seeded radioactivity Efficient distance! 1cm/3MeV In the practice 6-21 Mev => 2-7 cm treatment of superficial tumours γ : external radiation source Site of absorption sites of ionization = site of radiation damages Penetration distance is energy dependent γ-knife: focused dose of radiation about 200 portals in a specifically designed helmet e.g., 60 Co Eγ MeV, about TBq activity Treat tumours and lesions in the brain X/ray: The X-rays are generated by a linear accelerator. Few MeV photon energy. α β - e- γ, Rtg, p : n Would be ideal, but very expensive!
Neutron radiation:collision of high energy protons (66 MeV) into berillium target ( p(66) +Be) α β - Neutrons induce nuclear reactions. e- γ, Rtg, P, n: High LET Primery ionization LET Radiation Energy(MeV): LET(keV/µm): high low Typical LET values α particles fast neutron s protons X-rays 60-Co γ radiation β particles accelerated electrons 5.0 6.2 2.0 0.2 1.25 2.0 10.0 90 21 17 2.5 0.3 0.3 Damjanovich, Fidy, Szöllősi: Medical biophysics II. 3.2.3 3.2.4 3.2.5 VIII. 3.2 VIII. 4.4 IX.3